Returning to the starting point, how did your academic interest in the field of Pharmaceutical Sciences, and specifically in its intersection with nanotechnology, emerge, and how did you navigate your academic and research path?
My academic journey did not differ from the path followed by most Portuguese students in the 1990s. At the age of sixteen, I certainly did not have the fictional idea of choosing an academic and scientific path that would allow me to make a positive contribution to society and promote scientific and technological development. Although somewhat autonomously, it was a matter of chance. I came into contact with the area of nanotechnology while studying for a Master's degree that was part of the training offered by FFUP (where I enrolled after studying at FFUC [Faculty of Pharmacy of the University of Coimbra]), under the guidance of Dr. Carlos Maurício Barbosa, former president of the Portuguese Pharmaceutical Association, who was teaching a course entitled “Drug Vectorization” at the time. The subject fascinated me from the very first moment. And because it was so innovative at the time, it sparked my increased interest in conducting experimental work in this area. After completing that Master’s, I moved to Freie Universität Berlin, in Germany, where I remained during my PhD and postdoc, working with the inventor of solid lipid nanoparticles, Prof. Rainer H. Müller. Since then, my research has focused, though not exclusively, on refining this type of "drug vector" to overcome biological barriers and, more recently, to develop strategies for personalized medicine. It is a constant challenge, not only due to the increasing number of new compounds resulting from biotechnology but also because of the emerging introduction of Artificial Intelligence in the discovery of new drugs, the design of new pharmaceutical forms, and even in predicting the fate of these new pharmaceutical products in the environment.

The marriage between nanotechnology and pharmaceutical sciences is a prime example of how different fields of study can intersect, simultaneously promoting scientific development across various domains. Regarding this disciplinary intersection, how has this synergy contributed to pharmaceutical scientific progress and, by extension, how does it ultimately impact the field of health?
Although traditionally considered distinct disciplines, scientific evidence over the last 20 years shows that it is possible to create value by combining these two areas of knowledge. I can give you some examples, starting with the very first drug on the market employing nanotechnology - Doxil® - which received FDA (Food and Drug Administration) approval in 1995 for the treatment of Kaposi's Sarcoma. Doxil® is composed of Stealth® liposomes that carry about 10,000 molecules of doxorubicin. The encapsulation promoted by the phospholipid bilayer of the liposomes minimizes side effects such as cardiotoxicity, neutropenia, myelosuppression, vomiting, and alopecia, which are associated with high doses of this anthracycline in its free state (i.e., not encapsulated). A more recent example is the case of vaccines developed to prevent COVID-19 caused by SARS-CoV-2, specifically those from Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273), which are based on lipid nanoparticles for mRNA delivery.
Indeed, biotechnology and nanotechnology, which were once vague concepts to the general population, have become a collective and individual concern since the 2020 pandemic, and a priority for sustainable economies aimed at addressing global health and environmental goals. The European Commission itself recognizes the contribution of pharmaceutical nanotechnology to the modernization of industries in Member States through its applications in a variety of industrial and primary sectors, such as healthcare, with particular emphasis on the treatment of metabolic diseases like diabetes and neurodegenerative diseases such as Alzheimer's and Parkinson's diseases.

Much of the research you conduct has a particular focus on the design, development, and characterization of new drug delivery systems. Could you elaborate on the specific methodologies and techniques you use in this process, and perhaps highlight recent advancements or discoveries in the field that have significantly influenced your work?
When it comes to new drug delivery systems at the nano scale, the concept of what is considered 'nano' and the accurate characterization of this dimension is the most important challenge that researchers face. It happens that, when defining what nanomaterials are in general, the answer greatly depends on the community being asked. Historically, nanomaterials were first defined by physicists and materials scientists. Today, most definitions of what is considered a nanomaterial are based on the specific physical properties of the 'nano' dimension, such as optical and electronic properties, which are typically observed below 100 nm. In an attempt to harmonize regulation, in 2011, the Commission issued the Recommendation 2011/696/EU regarding the definition of nanomaterial, which was updated in 2022 by the Recommendation 2022/C 229/01, defining it as comprising solid particles with at least one external dimension smaller than 1 nm within the collection of nanoparticles, compared to the threshold of 50% if at least one of the other dimensions exceeds 100 nm. By excluding non-solid particles from this definition, a problem arises in categorizing micelles, liposomes, nanoemulsions, etc. Furthermore, there are challenges associated with producing nanoparticles under Good Manufacturing Practices, scaling up, and addressing occupational and environmental safety risks. The ethical issues inherent to 'nano' scale research pose an additional challenge in the context of Responsible Research and Innovation, leading to the rise of  a new discipline known as Nanoethics, which has gained relevance in the specialist colleges in which I participate.

You've been involved in numerous research projects. Could you highlight one or two particularly interesting or rewarding projects, also emphasizing their scientific relevance and impact on public and individual health?
Following what I mentioned about the priority the European Commission gives to projects focused on neurodegenerative diseases, I can highlight a collaborative effort with the University of Barcelona, which earned us the prestigious Jorge Heller Award from the Controlled Release Society. We developed a new type of double-loaded particles (with a flavonoid and an antioxidant) which, using Stealth® technology, significantly reduced neuroinflammation and cortical levels of beta-amyloid peptide in animal models of Alzheimer’s disease. This study reinforces the importance of our nanoparticles for treating chronic neurological diseases. In the context of acute treatment, I can refer to another project in collaboration with the Arbuzov Institute in Kazan, this time using solid lipid nanoparticles for treating brain poisoning caused by organophosphates. Organophosphates inhibit acetylcholinesterase, resulting in the accumulation of acetylcholine in the synapse. The excess of this neurotransmitter leads to a series of potentially fatal side effects. The available treatments are ineffective, the pralidoxime derivatives in use trigger erratic responses to organophosphates and, due to their positive charge, do not cross the blood-brain barrier, making them unable of reactivating phosphorylated acetylcholinesterase in the central nervous system. Using the same Stealth® technology, we developed a new type of nanoparticles loaded with two of these derivatives (one hydrophilic and one hydrophobic). We not only demonstrated the ability to reactivate the enzyme in the brain but also confirmed the effectiveness of this new formulation for the prophylaxis of poisoning.

Alongside research and teaching, you've also developed work in consulting on pharmaceutical technology and nanotechnology, particularly in the field of intellectual property and patents. In your opinion, what considerations and reflections should researchers prioritize when registering patents and managing intellectual property?
I share the view that those involved in the inventive process of developing new therapeutic systems, or new pharmaceutical forms, should have a thorough understanding of the state of the art, be capable of generating intellectual property, and also of promoting the transfer of that technology. It is not only natural but also expected that, as experts in the field, we are confronted with requests for consulting on patents and other technical documents to assess their inventiveness. This aspect of scientific research is particularly relevant when technical and non-technical information expands rapidly in scientific literature and the media, in different languages. It is not therefore uncommon to receive requests for translations into Portuguese of specialized documentation from German, English, and Spanish. If you search for the term 'Nanotechnology' in the Scopus database, for example, you will find nearly two million articles published worldwide. Only in the field of Pharmacy and Medicine, the number of publications in nanotechnology increased in the last decade from just over 30,000 articles in 2014 to more than 180,000 in 2024 (first quarter). These figures reflect the relevance of pharmaceutical nanotechnology for academics, clinicians, and the pharmaceutical industry. The same trend is observed with the submission of patent applications for products resulting from pharmaceutical nanotechnology, i.e., there is an exponential growth in applications, the majority of which come from the pharmaceutical industry.

You've completed your PhD in Pharmaceutical and Biopharmaceutical Nanotechnology at Freie Universität Berlin, Germany. How has your international academic experience shaped your approach to research and your perspective on the global landscape of pharmaceutical technology and nanotechnology?
I was fortunate to be welcomed into the 'Arbeitskreis' of Prof. Rainer H. Müller—a legendary figure in nanotechnology—in this highly distinguished working group, both scientifically and culturally. I interacted with professors and researchers from various generations and nationalities, from whom I gained lifelong lessons, as well as the experience of working on projects linked to the pharmaceutical industry (e.g., Schering AG) and the clinical sector (e.g., Charité Universitätsmedizin Berlin). I was also privileged to co-supervise my then 'Doktorvater’s' students in my area of expertise, which naturally contributed to developing and enhancing the necessary skills to conduct independent research, secure competitive funding, and, above all, lead and manage qualified and diverse human resources.

You are included in the 2023 edition of the 'Highly Cited Researchers' index for the second consecutive time, an initiative by Clarivate that annually recognizes the most influential scientists globally. Could you share with the scientific community at U.Porto your perspective on ensuring the production of high-quality, rigorous, and relevant research?
I recognize that the disciplinary area of nanotechnology, besides being emerging, particularly for developing personalized medicine, generates interest among the scientific community and the public in general, and product development requires a degree of creative talent. I believe that one can only think about the future with a deep understanding of the past.

Considering your prolific scientific career, what advice, guidance, or ideas would you share with young researchers who are just starting their research journeys?
From my experience working with multidisciplinary teams and in distinct geopolitical contexts, not only in Europe but also with institutions in the Middle East, Asia, North America, and South America, I recognize the priceless value of mobility for a researcher. Scientific development today does not accommodate basic tasks confined to a single group or institution. I have witnessed, not infrequently, circumstances where several Master’s and PhD students have been prevented by their supervisors from exchanging experiences and daily challenges of laboratory work with their peers. My students and researchers are made aware from the very beginning to the value of merit and individual initiative, often poorly received in our society, instead of the pernicious effects of endogamy. I support the view that mobility to foreign institutions should not only be promoted but made mandatory for both supervisees and supervisors.

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